title: The effects of levosimendan and glibenclamide on circulatory and metabolic variables in a canine model of acute hypoxia.
abstract: OBJECTIVE
  To study the effects of pretreatment with levosimendan (LEVO, a Ca²(+)-sensitizer and K (ATP) (+) channel opener) and/or the K (ATP) (+) channel antagonist glibenclamide (GLIB) on systemic hemodynamics, metabolism, and regional gastromucosal oxygenation during hypoxic hypoxemia.
  
  
  METHODS
  Chronically instrumented, healthy dogs (24-32 kg, n = 6 per group, randomized cross-over design) were repeatedly sedated, mechanically ventilated (FiO₂ ~0.3) and subjected to the following interventions: no pretreatment, LEVO pretreatment, GLIB pretreatment, or combined LEVO + GLIB pretreatment, each followed by hypoxic hypoxemia (FiO₂ ~0.1). We measured cardiac output (CO, ultrasonic flow probes), oxygen consumption (VO₂, indirect calorimetry), and gastromucosal microvascular hemoglobin oxygenation (μHbO₂, spectrophotometry).
  
  
  METHODS
  data are presented as mean ± SEM and compared by one-way ANOVA (direct drug effects within group) and two-way ANOVA (between all hypoxic conditions) both with Bonferroni corrections; p < 0.05.
  
  
  RESULTS
  In LEVO-pretreated hypoxemia, CO was significantly higher compared to unpretreated hypoxemia. The increased CO was neither associated with an increased VO₂ nor with markers of aggravated anaerobiosis (pH, BE, lactate). In addition, LEVO pretreatment did not further compromise gastromucosal μHbO₂ in hypoxemia. After combined LEVO + GLIB pretreatment, systemic effects of GLIB were apparent, however, CO was significantly higher than during unpretreated and GLIB-pretreated hypoxemia, but equal to LEVO-pretreated hypoxemia, indicating that GLIB did not prevent the increased CO in LEVO-pretreated hypoxia.
  
  
  CONCLUSIONS
  LEVO pretreatment resulted in improved systemic circulation (CO) during hypoxemia without fueling systemic VO₂, without aggravating systemic anaerobiosis markers, and without further compromising microvascular gastromucosal oxygenation. Thus, LEVO pretreatment may be an option to support the systemic circulation during hypoxia.
authors.affiliation: Department of Anaesthesiology, VU University Medical Center, Amsterdam, The Netherlands. L.Schwarte@vumc.nl
authors.forename: Lothar A
authors.initials: LA
authors.lastname: Schwarte
authors.forename: Ingo
authors.initials: I
authors.lastname: Schwartges
authors.forename: Kai
authors.initials: K
authors.lastname: Thomas
authors.forename: Patrick
authors.initials: P
authors.lastname: Schober
authors.forename: Olaf
authors.initials: O
authors.lastname: Picker
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005905:Glyburide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism*; D008660:Metabolism / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D023421:Models, Animal; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D006835:Hydrazones; D007004:Hypoglycemic Agents; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan; D000255:Adenosine Triphosphate; D005905:Glyburide